Trial record 4 of 12 for:    hong proton | Open Studies | Exclude Unknown

Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01821729
First received: March 27, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

This is a Phase II clinical trial, which tests the safety and effectiveness of an investigational combination of drugs to learn whether the combination of drugs works in treating a specific cancer. "Investigational" means that the combination of drugs is being studied. It also means that the FDA has not yet approved it for your type of cancer. Proton beam radiation therapy is an FDA approved radiation delivery system.

Conventional radiation therapy uses photons to treat cancer before patients undergo surgery to remove the tumor. In this study we are using radiation with protons, which spares surrounding tissue and organs from radiation. Proton radiation delivers radiation to the area requiring radiation with no dose beyond the treatment area. This may reduce side effects that patients would normally experience with conventional radiation therapy.

Researchers in the laboratory have discovered pathways inside cancer cells which contribute to the growth and survival of tumors. The FOLFIRINOX chemotherapy regimen is a combination of the drugs 5-fluorouracil, leucovorin and oxaliplatin. These chemotherapy drugs, along with the chemotherapy drug capecitabine, work by blocking these pathways and thereby preventing tumor growth. Capecitabine is FDA approved to be used alone or with other drugs to treat other types of advanced cancer, but not pancreatic cancer. In past research studies, FOLFIRINOX followed by radiation therapy with capecitabine has been identified as the most effective and active chemotherapy for patients with cancer that is spreading, and this is why we are using it to treat your type of cancer.

Losartan is classified as an angiotensin-receptor blocker (ARB), and is FDA approved for use in people with high blood pressure. Recent studies in people with different types of cancer, including pancreatic cancer, have shown that combining chemotherapy drugs with an ARB can help reduce/stop tumor growth more effectively than chemotherapy alone. Losartan has been used in previous research studies, and information from those research studies suggests that this drug in combination with FOLFIRINOX and capecitabine may be better at treating your type of cancer.

In this research study, we seek to determine whether combining FOLFIRINOX with Losartan before proton radiation therapy will be more efficient at controlling the growth of or shrinking your tumor than just FOLFIRINOX alone.


Condition Intervention Phase
Pancreatic Cancer
Drug: FOLFIRINOX
Drug: Losartan
Radiation: Proton Beam Radiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Feasibility Study of FOLFIRINOX-Losartan Followed by Accelerated Short Course Radiation Therapy With Proton Beam for Locally Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Feasibility of combining FOLFIRINOX-Losartan [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the feasibility of the combination of FOLIRINIOX-Losartan in patients with locally advanced unresectable pancreas cancer determining the proportion free of radiographic progression at the time of restaging and consideration of proton therapy after induction chemotherapy


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the progression free survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan and proton beam radiation therapy

  • Overall Survival for FOLFIRINOX + Proton Beam Radiation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine overall survival in patients treated with preoperative FOLFIRINOX and proton beam radiation therapy

  • Overall Survival for FOLFIRINOX Without Proton Radiation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the overall survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan without proton radiation (i.e. patients who demonstrate progression at restaging)

  • Determine Toxicity FOLFIRINOX-Losartan [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the toxicity of FOLFIRINOX-Losartan in patients with locally advanced pancreatic disease

  • Determine Toxicity of FOLFIRINOX-Losartan and Proton Beam Radiation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the toxicity of FOLFIRINOX-Losartan and proton beam radiation in patients with locally advanced pancreatic cancer.

  • Rate of Downstaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the rate of downstaging to surgical resection of FOLFIRINOX-Losartan followed by proton radiation in patients with locally advanced pancreatic cancer

  • Determine correlation of Somatic Gene Mutations and Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the correlation between a panel of somatic genetic mutations (SNaPSHOT) and outcome in locally advanced pancreatic cancer treated with FOLFIRINOX-Losartan +/- proton beam radiation/capecitabine

  • Determine Correlation Between Circulating Biomarkers and Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the correlation between circulating biomarkers of TGF-B1 downregulation, including circulating Collagen I levels, and outcome in locally advanced pancreatic cancer treated with FOLFIRINOX-Losartan +/- proton beam radiation/capecitabine.


Estimated Enrollment: 32
Study Start Date: July 2013
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Arm
FOLFIRINOX, Losartan, Proton Beam Radiation Therapy
Drug: FOLFIRINOX
Oxaliplatin via IV on Day 1 over 2 hours; Irinotecan via IV on Day 1 over 90 minutes, 5FU via IV on Day 1 over 2-4 minutes
Other Names:
  • 5-Fluorouracil
  • 5FU
  • Leucovorin
  • Oxaliplatin
Drug: Losartan
Taken orally every day during Phase I for all 8 cycles
Radiation: Proton Beam Radiation
30-45 minutes per day, daily Monday-Friday

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cytologic or histologic proof pancreatic ductal carcinoma
  • Locally advanced, unresectable disease
  • Life expectancy of at least 3 months

Exclusion Criteria:

  • Evidence of metastatic disease
  • Pregnant or breastfeeding
  • Serious concomitant systemic disorders incompatible with the study
  • Already treated on ACE or ARB therapy for hypertension or renal protection at the time of enrollment
  • Baseline hypotension
  • Prior chemotherapy, radiation therapy, or biologic therapy for treatment of pancreatic tumor
  • Treatment for other invasive carcinomas within the last 5 years (carcinoma in-situ is allowed)
  • Other serious uncontrolled medical conditions
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
  • Known, existing coagulopathy
  • Prior systemic fluoropyrimidine therapy
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment
  • History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance or oral drug intake
  • Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment
  • Taking cimetidine
  • Receiving other study agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, irinotecan, oxaliplatin or losartan
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01821729

Contacts
Contact: Theodore Hong, MD 6177267559 tshong1@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
Contact: Theodore Hong, MD    617-726-7559    tshong1@partners.org   
Principal Investigator: Theodore Hong, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Theodore Hong, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Theodore Sunki Hong, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01821729     History of Changes
Other Study ID Numbers: 13-051
Study First Received: March 27, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Locally Advanced

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Fluorouracil
Oxaliplatin
Losartan
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on August 28, 2014